3-Phenyl-3-dimethylaminoalkyl-4,4-dimethylpiperidin-2,6-diones of the following Formula I and their acid addition salts have been known since 1974 (see BE-A-808,958; corresponding to GB-A-1,455,687 & U.S. Pat. No. 3,963,729):

wherein:
R1 represents methoxy, ethoxy or hydroxy;
R2 represents methoxy, ethoxy, hydroxy or hydrogen; and
n represents 2 or 3.
They have been reported to have a range of pharmacological activities (see U.S. Pat. Nos. 3,963,729; 4,461,771; 4,738,973; 4,835,151; 4,835,151; 4,918,084; 4,994,475; 5,1177,086; GB-A-2,196,251 & GB-A-2,206,491) but were primary of interest for the treatment of stress-related affective disorders, especially anxiety and depression. They are the only compounds presently known to block selectively the activation of tryptophan hydroxylase induced by depolarisation, metabolic inhibitors, methyl xanthine, or stress. The compound of choice for clinical investigation was 3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4,4-dimethylpiperidine-2,6-dione, which has been variously identified as AGN 2979 (which designation will be used in this application); BTG 1501; MDL 72415 and SC 48274. A large number of acid addition salts of AGN 2979 have been proposed but the hydrochloride has been the salt of choice because hydrochloride acid addition salts are the most commonly used acid addition salts and can be readily and inexpensively prepared and there was no reason to believe that any other salts would have any advantage over the hydrochloride. There has been no previous proposal or suggestion to use a pamoate salt of AGN 2979, or of any other base of Formula I or other 3-phenyl substituted-3-dialkylaminoalkyl-4,4-dialkylpiperidin-2,6-dione, for any purpose.
A number of papers relating to clinical trials of the hydrochloride salt of AGN 2979 have been conducted and the results published. These showed the salt to be effective in the treatment of anxiety and depression at about 4 mg/kg/day (200-400 mg/day for human patients). However, a 1-year sub-acute toxicity study of the hydrochloride (200 mg/kg/day p o. (i.e. by mouth)) in rats showed that the animals suffered an immediate and continuing weight loss (40% over the 1-year period) and, as revealed by post-mortem examination, hepatocyte changes which had not been detected by routine transaminase determinations during the year. As a result, the USA Food and Drugs Administration (“F.D.A”) precluded the use of the dose levels previously used in the clinical trials. A subsequent clinical study by Cutler et al using an F.D.A. allowed dose of 1 mg b.i.d. (i.e. twice daily) (about 30 μg/kg/day) showed that the hydrochloride salt of AGN 2979 possessed only marginally effective anxiolytic properties at FDA permitted dose levels.